WOMEN 'S HEALTH AND MENOPAUSE : - National Heart, Lung ...

strual correlates of colorectal cancer risk are inconclusive.
Moderate inverse associations with parity
and OC use have been reported, but a favorable
role of later age at menopause is still
unclear. 131,143,144
Additional research is needed to confirm a potentially
favorable effect of HRT on colorectal cancer.
In Western countries, the numbers of deaths from
colorectal and breast cancers in women aged 55 or
older are similar (27,000 and 34,000, respectively,
in 1994 in the United States). 145 Thus, a decrease in
incidence or mortality from colorectal cancer could
greatly affect the balance of risks and benefits
associated with the use of HRT.
6. OTHER NEOPLASMS
A cohort study in Sweden of 23,244 women followed
for 6.7 years suggested a slight excess risk
of lung cancer related to the use of estrogen (RR =
1.3, 95 percent CI 0.9–1.7). 90 No information was
available on the duration of use or any other risk
factors. Two case-control studies in the United
States have also examined the relationship between
HRT use and risk of adenocarcinoma of the lung.
One study of 181 cases found a 70-percent excess
risk among HRT users, with the risk increasing to
a twofold risk for users who had started treatment
25 or more months previously. 146 In another casecontrol
study (N = 336 and 336), no substantial
relationship was found between HRT use and risk. 147
In the Swedish cohort study mentioned above, 90 a
total of 13 cases of biliary tract and liver cancers
were observed versus 31.7 expected, corresponding
to a RR of 0.4 (95 percent CI 0.2–0.7). In an
Italian case-control study, based on 82 histologically
confirmed cases of primary liver cancer and 368
control subjects, a decrease in risk related to HRT
was also noted (OR = 0.2, 95 percent CI 0.03–1.5). 148
However, no relationship between conjugated
estrogen and other estrogen use and hepatocellular
carcinoma was observed in another population
case-control study involving 74 cases and 162 population
controls from Los Angeles County; 149 the
RR was 1.1 for ever use, and 1.0 for > 5 years of
use. These data are not consistent with an adverse
effect of HRT on hepatocellular carcinoma.
Effects of HRT on other cancers, including stomach,
pancreas, and skin melanoma, are inconsistent. 20 A
suggestion of an inverse relation between HRT use
and cervical cancer 150 requires confirmation.
7. OTHER THERAPEUTIC APPROACHES
Given the recognized adverse effects of HRT,
much recent attention has focused on assessing
alternative approaches to treating the menopause,
including use of tamoxifen and other SERMs.
These agents (see also ch.7) are recognized estrogen
antagonists at selected target sites, such as
breast, while they behave as estrogen agonists in
different organ systems (e.g., bone). This may
offer many of the same advantages as HRT, while
eliminating some of the disadvantages (e.g.,
increase in the risk of breast cancer), which, in
fact, seem to be substantially reduced based on
available data.
In the National Surgical Adjuvant Breast and
Bowel Project (NSABP), a total of 13,388 U.S.
women who were 60 years of age or older or who
had a 5-year risk of 1.66 percent or more of developing
breast cancer or who had a history of lobular
carcinoma in situ were randomly assigned to
receive 20 mg daily of tamoxifen or placebo for 5
years. 151 After 69 months of followup, women
receiving tamoxifen had a 49 percent lower risk of
invasive breast cancer than placebo-treated
women. This beneficial effect of tamoxifen applied
to women of all ages and was particularly evident
in women with a history of lobular carcinoma in
situ or atypical hyperplasia. The reduction in risk
was limited to ER-positive tumors. Adverse effects
of tamoxifen, however, included excess risks of
endometrial cancer, stroke, pulmonary embolism,
and deep-vein thrombosis, events that occurred
more frequently in women aged 50 years or older.
241